1. Field of the Invention
The present invention relates to a therapy of renal diseases characterized by alterations of the kidney function, such as Chronic Kidney Disease (CKD), acute and chronic renal impairment, particularly, but not limited to, renal diseases that develop in diabetic patients or who underwent an anticancer chemotherapic treatment with a platinum derivative, and more generally, cytotoxic drugs at the kidney level for treating neoplastic diseases.
2. Description of the Related Art
Chronic Kidney Disease and the resulting renal impairment are extremely frequent diseases, even if they are under-diagnosed; in fact, it is estimated that they affect 17% of adult population.
The most frequent renal disease is characterized by an injury to the renal glomeruli.
Renal diseases may be hereditary or acquired; particularly, the acquired diseases may have a different etiology:                Immunologic, such as Goodpastures' syndrome, Lupus nephritis, and Immunoglobulins A nephropathy. In the case of the immunologically-mediated renal disease, its cause is the presence of a strong antigenic stimulus that elicits an immune reaction;        Dismetabolic, and particularly Diabetic nephropathy, one of the most frequent causes for chronic renal impairment. Prevalence is 20-30% in patients affected by type 1 Diabetes and about 10% in cases of type 2 Diabetes. It is a deceitful disease, since it is characterized by a particularly slow outbreak (up to 20-30 years from Diabetes outbreak) and essentially asymptomatic for a long period; it initially exhibits with a microalbuminuria (amount of albumin in the urine ranging between 30 and 300 mg/1), which slowly evolves toward macroalbuminuria, indicative of an established nephropathy (amount of albumin in the urine above 300 mg/1, until reaching values of 3 g in the 24 hours);        haemodynamic, from arterial hypertension. An alteration in the mechanisms of the kidney blood stream pressure leads, over time, to a decrease in the kidney filtering ability;        ischemic. Renal ischemia is the pathogenetic event most frequently involved in the acute renal impairment and the resulting tubular necrosis, in both native and transplanted kidneys;        toxic. Many of the clinically significant drugs (cytotoxic, chemotherapic agents, non-steroideal anti-inflammatory drugs, corticosteroid therapies, etc.) and several chemicals (such as radiologic contrast means, solvents, etc.) cause nephrotoxicity, which is able to very frequently cause a renal parenchyma inflammation and both transient and chronic functional impairment.        
Also in veterinary medicine, renal diseases which will evolve toward a chronic renal impairment compose a important clinical niche, representing the second cause of death in dogs, after tumoral diseases, and the first cause of death in older cats. From an etiology viewpoint, the causes determining the progressive and irreversible loss of functionality of nephrons in small animals were precisely classified (Squires et al, 1998) in:                Degenerative: interstitial chronic nephritis; kidney infarction        Autoimmune: glomerulonephritis from anti-glomerular Abs        Metabolic: Diabetes; hyperthyroidism (cat); hypercalcemia        Neoplastic: renal lymphomas and carcinomas        Idiopathic: amyloidosis; idiopathic-based glomerulonephrites        Infective: bacterial pielonephrites; Lyme nephropathy (Borreliosis)        Immuno-mediated: glomerulonephritis from immuno-complexes        Toxic: nephrotoxic drugs (e.g. cisplatin, amino glycosides, NSAIDs)        Traumatic: bladder and urethra rupture.        
One of the major targets of nephrology is, firstly, to understand the mechanism regulating the passage from an acute kidney injury to fibrotic Chronic Kidney Disease, since, once fibrogenesis has started, it may be currently very difficult to intervene on the fibrotic process; in any case, the target to stop or at least slow down the progression of Chronic Kidney Disease remains extremely relevant, in view that such a disease also constitutes an important risk factor for cardiovascular diseases. In this regard, many studies are under way to precisely understand the most relevant outbreak mechanisms, aiming to prevent those phenomena determining the irreversibility of this disease.
In spite of the number of new acquisitions on the pathogenic mechanisms involved in the development of the renal diseases, still no satisfactory therapeutic options exist for controlling these conditions.
Palmitoylethanolamide (PEA) is the progenitor of a family of N-acylamides called ALIAmides: a class of endogenous lipid molecules capable of normalizing the activity of immune cells by a local antagonist-type mechanism. Clinically, oral intake of PEA-containing products is able to improve neuropathic symptoms related to the peripheral neuropathy, while promoting a functional recovery of motor conduction velocity. PEA, at an experimental level, has shown to be efficient also in dismetabolic neuropathies, particularly, the administration thereof in an animal model of diabetes by streptozotocin suppresses allodynia and induces a partial body weight recovery and an increase in blood insulin levels.
Similarly to PEA, certain N-acylamides, generally formed by monoethanolamine and saturated and not saturated dicarboxylic fatty acids, not being per se physiologic, yet capable of forming, in their catabolism, substance that are found physiologically in the mammal's body, while not causing any build-up and/or toxicity, showed to be capable of causing pharmacological effects that are similar to the progenitor PEA.
The activity of PEA and other ALIAmides in the treatment of renal diseases has been already described by the Applicant in the European Patent Application Publication No. 2444078 A1, published on Apr. 25, 2012.
Silymarin is an extract of the plant Silybum marianum, also known as milk thistle, the activity of which in the treatment of liver diseases is known.